It is now generally recognized that the thymus gland controls the development and maintenance of the immune system by both endocrine and cellular components which contribute to initiating and maintaining the ability to combat invasions by pathogens or growth of neoplastic tissue and in preventing autoimmune disease. Our studies are based upon the previous isolation and partial purification of thymosin fraction 5, a family of polypeptides isolated from calf thymus, and the demonstration that these polypeptides can partially or fully reconstitute immune function in thymic-deprived animals and in humans with a number of primary immunodeficiency diseases or cancer. Of major potential importance to the goals of the National Cancer Program in the cancer treatment area is the recent completion of the first Phase II randomized trials, conducted by Dr. Richard Schulof here at The George Washington University Medical Center, showing that synthetic thymosin alpha1, when given in conjunction with radiotherapy of the lung, significantly prolonged the disease-free interval and resulted in early immune reconstitution. This is the first successful prospective randomized trial of immunotherapy in lung cancer using a synthetic thymic hormone. Our research has the following objectives: (1) to chemically characterize and determine the amino acid sequences of the peptide components of thymosin fraction 5, other than thymosin alpha1, that have immunoreconstitutive effects; (2) to develop and standardize large-scale procedures for the production of the biologically active peptides in fraction 5 adequate for human use; and (3) to determine in animal models the efficacy of these peptides in alleviating specific immunological defects.